Family screening in patients with isolated bicuspid aortic valve

Netherlands Heart Journal - To determine the prevalence of undiagnosed bicuspid aortic valve (BAV) and isolated aortic dilatation in first-degree relatives (FDRs) of patients with isolated BAV and...     

Diel activity patterns in overwintering Labrador anadromous Arctic charr

Hydrobiologia - Anadromous Arctic charr, Salvelinus alpinus, migrate back to freshwater in late summer to spawn and/or overwinter. While seasonal movement patterns during the freshwater residency...     

Differential effects of chronic agonist administration on mu-opioid receptor- and muscarinic receptor-regulated adenylate cyclase in rat striatal neurons.

In cultured rat striatal neurons exposed to 10 microM morphine or oxotremorine for 24 hours, we observed an increased (about 30%) dopamine D1 receptor-stimulated cyclic AMP production, whereas no desensitization of mu-opioid receptor or muscarinic cholinergic receptor was found. However, whereas upregulation of dopamine D1 receptor-stimulated adenylate cyclase activity upon 7 days morphine exposure was at least as pronounced as observed after 24 hours of exposure to the opioid, this adaptive phenomenon was virtually absent following one week of oxotremorine treatment. This reduced adenylate cyclase sensitization upon 7 days oxotremorine exposure appeared to coincide with desensitization of muscarinic cholinergic receptors. A possible role of the resistance of mu receptors to desensitization and the (resulting) upregulation of the neuronal adenylate cyclase system upon chronic receptor activation in the development of opiate tolerance and dependence is suggested.     

Quantitative analysis of Penicillium chrysogenum Wis54-1255 transformants overexpressing the penicillin biosynthetic genes

The low penicillin-producing, single gene copy strain Wis54-1255 was used to study the effect of overexpressing the penicillin biosynthetic genes in Penicillium chrysogenum. Transformants of Wis54-1255 were obtained with the amdS expression-cassette using the four combinations: pcbAB, pcbC, pcbC-penDE, and pcbAB-pcbC-penDE of the three penicillin biosynthetic genes. Transformants showing an increased penicillin production were investigated during steady-state continuous cultivations with glucose as the growth-limiting substrate. The transformants were characterized with respect to specific penicillin productivity, the activity of the two pathway enzymes delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS) and isopenicillin N synthetase (IPNS) and the intracellular concentration of the metabolites: delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV), bis-delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (bisACV), isopenicillin N (IPN), glutathione (GSH), and glutathione disulphide (GSSG). Transformants with the whole gene cluster amplified showed the largest increase in specific penicillin productivity (r(p))-124% and 176%, respectively, whereas transformation with the pcbC-penDE gene fragment resulted in a decrease in r(p) of 9% relative to Wis54-1255. A marked increase in r(p) is clearly correlated with a balanced amplification of both the ACVS and IPNS activity or a large amplification of either enzyme activity. The increased capacity of a single enzyme occurs surprisingly only in the transformants where all the three biosynthetic genes are overexpressed but is not found within the group of pcbAB or pcbC transformants. The indication of the pcbAB and pcbC genes being closely regulated in fungi might explain why high-yielding strains of P. chrysogenum have been found to contain amplifications of a large region including the whole penicillin gene cluster and not single gene amplifications. Measurements of the total ACV concentration showed a large span of variability, which reflected the individual status of enzyme overexpression and activity found in each strain. The ratio ACV:bisACV remained constant, also at high ACV concentrations, indicating no limitation in the capacity of the thioredoxin-thioredoxin reductase (TR) system, which is assumed to keep the pathway intermediate LLD-ACV in its reduced state. The total GSH pool was at a constant level of approx. 5.7 mM in all cultivations.     

Augmentation mammaplasty in male-to-female transsexuals

Hormonal therapy and gender-confirming surgery are the treatments of choice in appropriately selected male-to-female transsexuals. Penectomy and vaginoplasty are the paramount surgical requests of the male transsexual, but breast enlargement greatly increases subjective feelings of femininity. There are only limited reports on augmentation mammaplasty in male transsexuals, and hardly any attention has been paid to the differences between the female mammary anatomy and its male counterpart. The basic anatomic and surgical considerations of augmentation mammaplasty for 201 male-to-female transsexuals who were operated on from 1979 to 1997 are reviewed and discussed. They include the differences between male and female anatomy and how to feminize the male chest, the results of hormonal therapy and the proper timing of surgery, the choice of implant size and surgical approach, the results that may be expected after surgery, and the implications of all mentioned on the long-term outcome and follow-up after augmentation mammaplasty. Because the referring doctor may not check on the breasts or may not be trained to examine augmented breasts for pathologic conditions, the mammaplastic surgeon has an obligation to ensure the proper follow-up of these patients.     

Are men and women really so different?

Distinct differences in the behaviour and preferences of men and women have conventionally been attributed to Trivers' powerful insights regarding the impact of parental investment on sexual selection and mating systems. This has spawned a huge literature about the evolutionary significance of human sex differences. But are men and women really so different? An elegant new study shows that men and women are strikingly similar in their mate preferences. Have conventional models blinded us to the obvious, and precluded the posing of far more interesting questions?     

The Proteome Analysis database: a tool for the in silico analysis of whole proteomes

The Proteome Analysis database (http://www.ebi.ac.uk/proteome/) has been developed by the Sequence Database Group at EBI utilizing existing resources and providing comparative analysis of the predicted protein coding sequences of the complete genomes of bacteria, archeae and eukaryotes. Three main projects are used, InterPro, CluSTr and GO Slim, to give an overview on families, domains, sites, and functions of the proteins from each of the complete genomes. Complete proteome analysis is available for a total of 89 proteome sets. A specifically designed application enables InterPro proteome comparisons for any one proteome against any other one or more of the proteomes in the database.     

p116Rip is a novel filamentous actin-binding protein

p116Rip is a ubiquitously expressed protein that was originally identified as a putative binding partner of RhoA in a yeast two-hybrid screen. Overexpression of p116Rip in neuroblastoma cells inhibits RhoA-mediated cell contraction induced by lysophosphatidic acid (LPA); so far, however, the function of p116Rip is unknown. Here we report that p116Rip localizes to filamentous actin (F-actin)-rich structures, including stress fibers and cortical microfilaments, in both serum-deprived and LPA-stimulated cells, with the N terminus (residues 1-382) dictating cytoskeletal localization. In addition, p116Rip is found in the nucleus. Direct interaction or colocalization with RhoA was not detected. We find that p116Rip binds tightly to F-actin (Kd approximately 0.5 microm) via its N-terminal region, while immunoprecipitation assays show that p116Rip is complexed to both F-actin and myosin-II. Purified p116Rip and the F-actin-binding region can bundle F-actin in vitro, as shown by electron microscopy. When overexpressed in NIH3T3 cells, p116Rip disrupts stress fibers and promotes formation of dendrite-like extensions through its N-terminal actin-binding domain; furthermore, overexpressed p116Rip inhibits growth factor-induced lamellipodia formation. Our results indicate that p116Rip is an F-actin-binding protein with in vitro bundling activity and in vivo capability of disassembling the actomyosin-based cytoskeleton.     

Sympathetic control of the cardiovascular response to acute hypoxemia in the chick embryo

In response to an acute hypoxemic insult, the mammalian fetus shows a redistribution of the cardiac output in favor of the heart and brain. Peripheral vasoconstriction contributes to this response and is partly mediated by the release of catecholamines. Two mechanisms of catecholamine release in the fetus are reported: 1) neurogenic sympathetic stimulation and 2) a nonneurogenic mechanism via a direct effect of hypoxemia on chromaffin tissues. In the present study, the effects of sympathetic blockade on plasma catecholamine release and cardiac output distribution in response to acute hypoxemia were studied in the chick embryo at different stages of incubation. Only at the end of the incubation period, sympathetic blockade markedly attenuated the increase in plasma catecholamine concentrations and resulted in a greater fraction of the cardiac output distributed to the carcass. However, these effects did not prevent a significant increase in cardiac output to the brain and heart during acute hypoxemia. These data imply that in the chick embryo the contribution of neurogenic mechanisms to the catecholaminergic response to acute hypoxemia becomes greater by the end of the incubation period.